Heterogeneity of adult masseter muscle satellite cells with cardiomyocyte differentiation potential

Exp Cell Res. 2018 Oct 1;371(1):20-30. doi: 10.1016/j.yexcr.2018.05.028. Epub 2018 May 26.

Abstract

Although resident cardiac stem cells have been reported, regeneration of functional cardiomyocytes (CMs) remains a challenge. The present study identifies an alternative progenitor source for CM regeneration without the need for genetic manipulation or invasive heart biopsy procedures. Unlike limb skeletal muscles, masseter muscles (MM) in the mouse head are developed from Nkx2-5 mesodermal progenitors. Adult masseter muscle satellite cells (MMSCs) display heterogeneity in developmental origin and cell phenotypes. The heterogeneous MMSCs that can be characterized by cell sorting based on stem cell antigen-1 (Sca1) show different lineage potential. While cardiogenic potential is preserved in Sca1+ MMSCs as shown by expression of cardiac progenitor genes (including Nkx2-5), skeletal myogenic capacity is maintained in Sca1- MMSCs with Pax7 expression. Sca1+ MMSC-derived beating cells express cardiac genes and exhibit CM-like morphology. Electrophysiological properties of MMSC-derived CMs are demonstrated by calcium transients and action potentials. These findings show that MMSCs could serve as a novel cell source for cardiomyocyte replacement.

Keywords: Cardiac differentiation; Cranial masseter muscle; Regenerative medicine; Satellite cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Ataxin-1 / genetics
  • Ataxin-1 / metabolism
  • Biomarkers / metabolism
  • Calcium / metabolism
  • Cell Differentiation*
  • Cell Lineage / genetics
  • Gene Expression
  • Genes, Reporter
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Homeobox Protein Nkx-2.5 / genetics
  • Homeobox Protein Nkx-2.5 / metabolism
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Masseter Muscle / cytology*
  • Masseter Muscle / metabolism
  • Mice
  • Mice, Transgenic
  • Muscle Development / genetics*
  • Myocytes, Cardiac / cytology*
  • Myocytes, Cardiac / metabolism
  • PAX7 Transcription Factor / genetics
  • PAX7 Transcription Factor / metabolism
  • Phenotype
  • Red Fluorescent Protein
  • Regeneration
  • Satellite Cells, Skeletal Muscle / cytology*
  • Satellite Cells, Skeletal Muscle / metabolism

Substances

  • Ataxin-1
  • Atxn1 protein, mouse
  • Biomarkers
  • Homeobox Protein Nkx-2.5
  • Luminescent Proteins
  • Nkx2-5 protein, mouse
  • PAX7 Transcription Factor
  • Pax7 protein, mouse
  • Green Fluorescent Proteins
  • Calcium